The objective of the proposed work is to define the manner in which microfilariae penetrate the midgut wall of vector mosquitoes, thereby entering the hemocoel. In particular, we shall: (1) determine how microfilariae attain directional movement in blood ingested by mosquitoes. (2) Determine whether microfilariae maintain attachment to the midgut wall once they contact it. Further, we hope to define the nature of this attachment if it occurs. (3) Examine whether microfilariae penetrate through or between cells of the mosquito midgut. (4) Determine the site at which microfilariae penetrate the basement lamina of the mosquito midgut. (5) Identify where exsheathment of the microfilariae occurs. (6) Determine whether shed microfilarial sheaths enhance further development of the microfilariae. The project applies experimental and observational microscopic techniques to identify physiological features of microfilariae that facilitate vector invasion. Definitive information on this act of microfilarial penetration of mosquito midguts may provide a biological basis for controlling transmission, even extending to other arthropod-borne pathogens.